A porous biodegradable polymer scaffold is widely used as a matrix for regeneration of various tissues. The scaffold requires a porous structure having a high interconnectivity between pores so as to achieve a sufficient cell adhesion density and to facilitate supply of nutrition and oxygen for cell proliferation and cell differentiation.
There are various methods for preparing a porous biodegradable polymer scaffold. From among the methods, a porogen leaching method is most widely used. In the method, as the porogen, various particles such as salt, foaming salt, carbohydrate, or hydrocarbon wax may be utilized, and from a polymer/solvent/porogen mixture, porogen is selectively dissolved or foamed to form pores. In addition, there are other methods, such as emulsification/freeze-drying, phase separation, expansion of critical liquid phase, three-dimensional inkjet printing (A. G. Mikos, G. Sarakinos, S. M. Leite, J. P. Vacanti, R. Langer, Biomaterials, 14 (1993) 323-330; Z. Ma, C. Gao, Y. Gong, J. Shen, J. Biomed. Mater. Res. 67B (2003) 610-617; A. Park, B. Wu, L. G. Griffith, J. Biomater. Sci. Polym. Ed. 9 (1998) 89-110).
Such a porous polymer scaffold induces adhesion and differentiation of a cell, and thus may be usefully utilized for regeneration of bone, cartilage, and liver. However, such a scaffold is transplanted into a body through a surgical operation, thereby imposing a physical/economical burden on a patient. Accordingly, in order to minimize the inconvenience of a patient, a method for injecting a biodegradable polymer scaffold through a syringe has been developed. In this method, a polymer liquid including cells is injected so that a hydrogel can be formed through photocrosslink or sol-gel (J. j. Marler, A. Guha, J. Rowley, R. Koka, D. Monney, J. Upton, J. p. Vacanti, Plast. Reconstr. Surg. 105 (2000) 2049-2058; S. He, M. J. Yaszemski, A. W. Yasko, P. S. Engel, A. G. Mikos, Biomaterials, 21 (2000) 2389-2394).
However, such a hydrogel cannot provide an ideal environment for a cell required to be attached on a solid surface, and cannot protect cells contained therewithin due to its low mechanical strength. In order to solve such a disadvantage, a wide range of natural/synthetic microparticles, such as Cultispher (a microparticle prepared by a porous structural gelatin), are used for adhesion-dependent animal cell culture. However, they have a disadvantage in that biocompatibility is low, and mechanical strength is not satisfactory.
A currently used method for preparing microparticles for injection is an emulsification-solvent evaporation method. Especially, in a W/O/W double emulsification method, two emulsification steps are carried out. According to the stability of W/O emulsion in the first emulsification step, the porous structure is determined. The emulsion has a disadvantage in that its preparation is difficult, because it is thermodynamically unstable, and thus an aqueous phase and an organic phase show a tendency to be separated from each other through coalescence, fusion, creaming, etc. (M. Kanouni, H. L. Rosano, N. Naouli, Adv. Colloid Interface Sci. 99 (2002) 229-254; A. J. Webster, M. E. Cates, Langmuir, 14 (1998) 2068-2079).
Also, there is a method for preparing a microcarrier, the method consisting a W/O/W double emulsification step, in which an organic phase having an aliphatic polyester polymer dissolved therein is added with an aqueous solution having foamable salt dissolved therein so as to form W/O emulsion, and then the emulsion is emulsified by being re-dispersed in an aqueous solution including hydrophilic surfactant (Korean Patent No. 801194). The microcarrier has characteristics such as biodegradability, a high porosity, a high interconnectivity between pores, and disadvantages such as a low mechanical strength, difficulty in mass production.
Accordingly, it has been constantly required to develop a method for preparing a microparticle which can be injected through a syringe due to high physical properties (such as biocompatibility, biodegradability, porosity, mechanical strength) and the microcarrier's size-adjustability, and can be easily mass-produced.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.